Back to Search
Start Over
Adverse effects of free fatty acid associated with increased oxidative stress in postischemic isolated rat hearts
- Source :
- Molecular and Cellular Biochemistry. 283:147-152
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- The mechanisms of the adverse effects of free fatty acids on the ischemic-reperfused myocardium are not fully understood. Long-chain fatty acids, including palmitate, uncouple oxidative phosphorylation and should therefore promote the formation of oxygen-derived free radicals, with consequent adverse effects. Conversely, the antianginal agent trimetazidine (TMZ), known to inhibit cardiac fatty acid oxidation, could hypothetically lessen the formation of reactive oxygen species (ROS) and thus improve reperfusion mechanical function. Isolated perfused rat hearts underwent 30 min of total global ischemia followed by 30 min of reperfusion. Hearts were perfused with glucose 5.5 mmol/l or palmitate 1.5 mmol/l with or without TMZ (100 micromol/l). Ascorbyl free radical (AFR) release during perfusion periods was measured by electron spin resonance as a marker of oxidative stress. Post-ischemic recovery in the palmitate group of heart was lower than in the glucose group with a marked rise in diastolic tension and reduction in left ventricular developed pressure (Glucose: 85 +/- 11 mmHg; Palmitate: 10 +/- 6 mmHg; p0.001). TMZ decreased diastolic tension in both glucose- and in palmitate-perfused hearts. Release of AFR within the first minute of reperfusion was greater in palmitate-perfused hearts and in hearts perfused with either substrate, this marker of oxidative stress was decreased by TMZ (expressed in arbitrary units/ml; respectively: 8.49 +/- 1.24 vs. 1.06 +/- 0.70 p0.05; 12.47 +/- 2.49 vs. 3.37 +/- 1.29 p0.05). Palmitate increased the formation of ROS and reperfusion contracture. TMZ, a potential inhibitor of palmitate-induced mitochondrial uncoupling, decreased the formation of free radicals and improved postischemic mechanical dysfunction. The novel conclusion is that adverse effects of fatty acids on ischemic-reperfusion injury may be mediated, at least in part, by oxygen-derived free radicals.
- Subjects :
- Male
medicine.medical_specialty
Free Radicals
Vasodilator Agents
Clinical Biochemistry
Myocardial Ischemia
Trimetazidine
Ischemia
Myocardial Reperfusion Injury
Ascorbic Acid
Oxidative phosphorylation
Fatty Acids, Nonesterified
medicine.disease_cause
Internal medicine
medicine
Animals
Rats, Wistar
Molecular Biology
Beta oxidation
chemistry.chemical_classification
Reactive oxygen species
Fatty acid
Heart
Cell Biology
General Medicine
medicine.disease
Myocardial Contraction
Rats
Oxidative Stress
Endocrinology
Biochemistry
chemistry
Oxidation-Reduction
Perfusion
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 15734919 and 03008177
- Volume :
- 283
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biochemistry
- Accession number :
- edsair.doi.dedup.....f7c6addc7cdaeb363ea691f6d69df40a